Department of Neurology, Charité-Universitätsmedizin Berlin, Freie Universität Berlin, Humboldt-Universität Zu Berlin, and Berlin Institute of Health, Charitéplatz 1, 10117, Berlin, Germany.
Department of Experimental Neurology and Center for Stroke Research Berlin, Charité-Universitätsmedizin Berlin, Freie Universität Berlin, Humboldt-Universität Zu Berlin, and Berlin Institute of Health, Charitéplatz 1, 10117, Berlin, Germany.
Sci Rep. 2020 Oct 26;10(1):18215. doi: 10.1038/s41598-020-75209-z.
Glucose hypometabolism potentially contributes to Alzheimer's disease (AD) and might even represent an underlying mechanism. Here, we investigate the relationship of diet-induced metabolic stress and AD as well as the therapeutic potential of chia seeds as a modulator of glucose metabolism in the APP23 mouse model. 4-6 (pre-plaque stage, PRE) and 28-32 (advanced-plaque stage, ADV) weeks old APP23 and wild type mice received pretreatment for 12 weeks with either sucrose-rich (SRD) or control diet, followed by 8 weeks of chia seed supplementation. Although ADV APP23 mice generally showed functioning glucose homeostasis, they were more prone to SRD-induced glucose intolerance. This was accompanied by elevated corticosterone levels and mild insulin insensitivity. Chia seeds improved spatial learning deficits but not impaired cognitive flexibility, potentially mediated by amelioration of glucose tolerance, attenuation of corticosterone levels and reversal of SRD-induced elevation of pro-inflammatory cytokine levels. Since cognitive symptoms and plaque load were not aggravated by SRD-induced metabolic stress, despite enhanced neuroinflammation in the PRE group, we conclude that impairments of glucose metabolism do not represent an underlying mechanism of AD in this mouse model. Nevertheless, chia seeds might provide therapeutic potential in AD as shown by the amelioration of cognitive symptoms.
葡萄糖代谢不足可能导致阿尔茨海默病(AD),甚至可能是其潜在机制之一。在这里,我们研究了饮食诱导的代谢应激与 AD 的关系,以及奇亚籽作为 APP23 小鼠模型葡萄糖代谢调节剂的治疗潜力。4-6 周龄(斑块前阶段,PRE)和 28-32 周龄(斑块进展阶段,ADV)的 APP23 转基因和野生型小鼠接受了 12 周的富含蔗糖(SRD)或对照饮食预处理,随后补充 8 周的奇亚籽。尽管 ADV APP23 小鼠通常表现出正常的葡萄糖稳态,但它们更容易出现 SRD 诱导的葡萄糖不耐受。这伴随着皮质酮水平的升高和轻度胰岛素不敏感。奇亚籽改善了空间学习障碍,但没有改善认知灵活性,这可能是通过改善葡萄糖耐量、降低皮质酮水平以及逆转 SRD 诱导的促炎细胞因子水平升高来介导的。由于认知症状和斑块负荷没有因 SRD 诱导的代谢应激而加重,尽管 PRE 组的神经炎症增强,我们得出结论,葡萄糖代谢受损不是该小鼠模型 AD 的潜在机制。然而,奇亚籽可能通过改善认知症状提供 AD 的治疗潜力。